The idea of gender is introduced to most people early in their lives, usually when they are kids, and is typically based on their biological sex from birth. Masculine biology correlates with the “male” identity and feminine biology with the “female” identity. So from a young age, most of us are taught about the genders from a binary lens. The labels we are assigned then have a major impact on how we view ourselves and are socialized. As we explore these ideas of gender and sex it is important to ask ourselves the following questions. How does our biological sex get determined? What happens when there are anomalies during the sex-determination process?
You may have heard of DNA being referred to as the “blueprint of life.” DNA, deoxyribonucleic acid, is made up of four types of nucleotides that are strung together to code for various complex molecules that are needed for the structure, function and regulation of cells called proteins. In order to fit all the genetic material in a cell, DNA must be condensed to form chromosomes. Human cells have 46 chromosomes grouped into 23 pairs. One chromosome from each pair comes from the father’s sperm cell, and the other from the mother’s ovum (egg cell). During sexual reproduction, the sperm cell fertilizes and combines its genetic material with the ovum to form a zygote, a single-cell organism that has all 46 chromosomes. This zygote multiplies and divides, eventually becoming the multicellular human fetus. But how does this single-cell know whether to develop into a male or female embryo?
Primary sex determination (the initial process of determining sex) in mammals is dependent on the 23rd pair of chromosomes, known as the sex chromosomes “X” and “Y.” In typical development, XX chromosomes give rise to female biological characteristics, while XY gives rise to male. Consequently, the 23rd chromosome in an ovum can only be an “X” chromosome, while the 23rd chromosome in a sperm cell has a 50% chance of being either an “X” or “Y.” Thus, it is the sperm cell that determines the sex, and the embryo has an equal chance of being either male or female.
On a section of the Y chromosome, we can find the sex-determining region of the Y gene (SRY gene) which is critical for the formation of male sexual organs, such as the testis. As they develop, the testicles produce and secrete two hormones that are necessary for the continued development of male sex traits: anti-Müllerian duct hormone (AMH) and testosterone. The two hormones work simultaneously as the AMH is required to prevent the formation of female biological traits, while testosterone proceeds with the masculinization process. Therefore, it is the presence of the SRY gene on the Y chromosome that prevents an embryo from becoming female and allows it to become male.
However, the process of fertilization doesn’t always function as mentioned above. In fact, there are occasional errors in the formation of the ova, sperm cells and zygotes, resulting in Sex Chromosome Anomalies (SCA) characterized by any combination of sex chromosomes other than the XX or XY pairs.
Turner Syndrome (TS) is an SCA where the zygote is missing a sex chromosome and has only a single X, depicted as XO (“O” indicates a lack of chromosome). This occurs when either the sperm cell or ovum lacks a sex chromosome before fertilization. The absence of the second X or Y chromosome can result in growth issues and a whole host of other conditions like scoliosis, micrognathia (an undersized lower jaw), shorter leg length, hearing loss and heart defects. Turner Syndrome can reduce one’s lifespan by 13–15 years, mostly due to the associated cardiovascular conditions. TS can additionally cause primary and secondary amenorrhea (the absence of menstruation) which can result in infertility. Though TS has varying clinical presentations between patients, most individuals with Turner Syndrome tend to identify as female.
Another common sex chromosome anomaly is Klinefelter Syndrome (KS). People with KS have one or more extra X chromosomes, this is due to the sperm cell and/or ovum carrying the extra chromosomes before fertilization. So, instead of just the typical XY genotype, those with KS have XXY, XXXY or XXXXY genotypes. These individuals usually identify as male. The extra X chromosome(s) can cause testicular tissue to thicken and scar which may prevent sperm cell formation, leading to infertility. Approximately 3% of all male infertility cases are due to KS. As well, most individuals with this condition are taller, with smaller testes, larger breast tissue and azoospermia (spermless ejaculate). The severity of the clinical effects are dependent on the amount of extra X chromosomes. Most men with KS are diagnosed in their adolescence when being evaluated for tall stature, testis size or arrested puberty, or in their adulthood when evaluated for infertility.
While Turner and Klinefelter Syndromes are the most commonly discussed SCAs, others such as 46, XX male and 46, XY female syndromes are also prevalent. In these cases, individuals develop sex organs and characteristics that differ from their designated genetic sex. Premature sperm cells contain both the X and Y chromosomes which are separated during spermatogenesis (the formation of sperm cells). In 46, XX male syndrome, the X chromosome from the sperm cell carries a section of the Y chromosome with the SRY gene, a crossing-over event that occurs during a step in spermatogenesis. Since the zygote now has the SRY gene, masculinization of the embryo occurs. Like the other anomalies, the clinical presentation for this syndrome also varies, with some men depicting completely normal male structures.
Meanwhile, 46, XY female syndrome can occur from the lack of the SRY gene on the Y chromosome or due to Complete Androgen Insensitivity Syndrome (CAIS), where testosterone is produced but does not function. Other causes of 46, XY female syndrome include mutations in; the SRY gene, the genes regulating SRY gene expression and the SRY gene transcription pathway. Because testicular development and masculinization are impaired in any of these cases, most people with 46, XY female syndrome tend to identify as a woman. Individuals with these sex chromosome anomalies can undergo hormone therapy and other treatments to manage the effects of the syndromes.
Though human sexual development is largely determined by the X and Y chromosome patterns, the clinical presentation of sex organs and secondary sex characters can greatly differ from the genetics. It is not always true that an XY individual will present or identify as male, nor will an XX individual present as a female. People with a Sex Chromosome Anomaly may find gender-affirming support helpful, whether it be through psychosocial counselling, community support, medical treatments or surgical procedures. As we gain a better understanding of these anomalies and the challenges they pose, more questions may be raised. It is worth considering how such cases shape our broader understanding of gender and identity.